Synthetic carbohydrate-based anticancer vaccines: the Memorial Sloan-Kettering experience

Abstract

Malignantly transformed cells can express aberrant cell surface glycosylation patterns, which serve to distinguish them from normal cells. This phenotype provides an opportunity for the development of carbohydrate-based vaccines for cancer immunotherapy. Synthetic carbohydrate-based vaccines, properly introduced through vaccination of a subject with a suitable construct, should be recognized by the immune system. Antibodies induced against these carbohydrate antigens could then participate in the eradication of carbohydrate-displaying tumor cells. Advances in carbohydrate synthetic capabilities have allowed us to efficiently prepare a range of complex, synthetic anticancer vaccine candidates. We describe herein the progression of our longstanding carbohydrate-based anticancer vaccine program, which is now at the threshold of clinical evaluation in several contexts. Our carbohydrate-based anticancer vaccine program has evolved through a number of stages: monomeric vaccines, monomeric clustered vaccines, unimolecular multi-antigenic vaccines and dual-acting vaccines. This account will focus on our recently developed unimolecular multi-antigenic constructs and potential dual-acting constructs, which contain clusters of both carbohydrate and peptide epitopes.

Keywords::

• antibody
• anticancer vaccine
• carbohydrate antigen
• epitope
• glycoconjugate
• glycopeptide
• mucin
• oligosaccharide

Financial & competing interests disclosure

Support for this work was provided by the NIH (CA28824 to Samuel J Danishefsky). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.